A lethal perinatal cardiac phenotype resulting from altered integrin function in cardiomyocytes

Maria L. Valencik, Rebecca S. Keller, Joseph C. Loftus, John A. McDonald

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Background: Integrins are heterodimeric receptors that couple the extracellular matrix to intracellular signaling pathways and the cyoskeleton. Integrins are strain transducers and candidates for modulators or effectors of cardiac hypertrophy. Methods: To begin to probe this function, we have transgenically expressed a chimeric protein that alters integrin function in cardiomyocytes. The transgene (Tac-β1D) consists of the biologically inert extracellular and transmembrane domain of the interleukin-2 receptor α subunit (Tac) fused to the cytoplasmic tail of the human β1D integrin driven by the cardiac α-myosin heavy chain promoter. Transgene expression results in a severe, usually fatal, perinatal cardiac phenotype, characterized by initial electrocardiographic abnormalities followed by extensive myocyte loss, macrophage infiltration, and replacement fibrosis. Results: Expression of Tac-β1D resulted in displacement of endogenous β1D integrin from Z-lines and T-tubules, decreased expression of endogenous β1D, and disrupted the fibronectin pericellular matrix. These results are consistent with an essential role for β1 integrins in maintenance of cardiomyocyte viability and interaction with extracellular matrix. Conclusion: The appearance of conduction abnormalities before morphologic changes suggests that integrins are important in the development or maintenance of the conducting system of the heart.

Original languageEnglish (US)
Pages (from-to)262-272
Number of pages11
JournalJournal of Cardiac Failure
Issue number4
StatePublished - Aug 2002


  • Arrhythmia
  • Inside-out signaling
  • Myocardial disease
  • Transgenic mice

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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